ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2015
High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68 citing papers in PubMed, 117 citations in OpenAlex.
- Human Y chromosome pan-organ mapping reveals progressive mosaic loss from normal to cancer.JCI insight · 2026Article
- Clinical and translational roles of circulating tumor cells in non-small cell and small cell lung cancer: a narrative review.Journal of thoracic disease · 2026Review
- Chromosomal instability as a driver of cancer progression.Nature reviews. Genetics · 2025Review
- Mechanical stress during confined migration causes aberrant mitoses and c-MYC amplification.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Current and future applications of liquid biopsy in non-small-cell lung cancer-a narrative review.Translational lung cancer research · 2023Review
- Review
- Progress and application of circulating tumor cells in non-small cell lung cancer.Molecular therapy oncolytics · 2021Review
- Circulating tumour cells and circulating cell-free DNA in patients with lung cancer: a comparison between thoracotomy and video-assisted thoracoscopic surgery.BMJ open respiratory research · 2021Article
- Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms.Endocrine-related cancer · 2021Article
- The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.International journal of molecular sciences · 2021Review
- The Liquid Biopsy for Lung Cancer: State of the Art, Limitations and Future Developments.Cancers · 2021Review
- Applicability of liquid biopsies to represent the mutational profile of tumor tissue from different cancer entities.Oncogene · 2021Article
- Detection of circulating genetically abnormal cells using 4-color fluorescence in situ hybridization for the early detection of lung cancer.Journal of cancer research and clinical oncology · 2021Article
- Circulating tumor cell copy-number heterogeneity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors.NPJ precision oncology · 2021Article
- Clinical utility of circulating tumor cells: an update.Molecular oncology · 2021Review
- Circulating tumor cell profiling for precision oncology.Molecular oncology · 2021Review
- Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability.Cells · 2021Review
- Small Cell Size Circulating Aneuploid Cells as a Biomarker of Prognosis in Resectable Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Article
- Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond.British journal of cancer · 2021Review
- DNA Damage and Activation of cGAS/STING Pathway Induce Tumor Microenvironment Remodeling.Frontiers in cell and developmental biology · 2021Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. PATIENTS AND
methodsUsing isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration.
resultsROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN.
conclusionWe provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene abnormalities and elevated numerical CIN, a potential mechanism to escape ROS1-inhibitor therapy in ROS1-rearranged NSCLC tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.